{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T21:39:50Z","timestamp":1792532390477,"version":"4.5.0"},"reference-count":37,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T00:00:00Z","timestamp":1759795200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T00:00:00Z","timestamp":1759795200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:p>\n                    Momelotinib, a Janus kinase (JAK) 1\/JAK2\/activin A receptor type 1 inhibitor, is approved for the treatment of myelofibrosis with anemia. These analyses characterized the population pharmacokinetics of momelotinib and its active metabolite M21 following administration of the commercial tablet formulation in patients with myelofibrosis from phase II\/III trials and other participants from phase I trials (\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u2009661). Predicted covariate effects on momelotinib, M21, and total active moiety (TAM)\u2014representing the combined potency\u2010weighted exposures of momelotinib and M21\u2014exposures following 200\u2010mg once\u2010daily dosing were evaluated using a simulation\u2010based approach. Using sequential modeling, momelotinib was described by a two\u2010compartment model with six transit absorption compartments and first\u2010order elimination, and M21 by a two\u2010compartment model with first\u2010order elimination. Hepatic function, concomitant CYP3A4 inducers, and concomitant OATP1B1\/1B3 inhibitors were significant momelotinib covariates, while baseline creatinine clearance and hepatic function were significant M21 covariates, with cumulative effects on TAM. Exposure\u2013response relationships between the average TAM concentration under actual dosing and key efficacy and safety end points were assessed using data from the 24\u2010week randomized period of three phase III trials in patients with myelofibrosis (\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u2009417). After relevant covariate adjustment, significant positive relationships were identified with spleen volume reduction and transfusion independence (the latter specifically in JAK inhibitor\u2013experienced patients), but not symptom improvement. Greater TAM exposure was significantly associated with lower odds of grade 3\/4 anemia and higher odds of any\u2010grade peripheral neuropathy, although the latter was infrequently observed in phase III trials. There was no significant relationship with grade \u2265\u20093 thrombocytopenia or any\u2010grade diarrhea.\n                  <\/jats:p>","DOI":"10.1002\/cpt.70076","type":"journal-article","created":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T11:15:41Z","timestamp":1759835741000},"page":"629-640","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Population Pharmacokinetics and Exposure\u2013Response Analyses of Momelotinib, Its Active Metabolite (M21), and Total Active Moiety in Myelofibrosis"],"prefix":"10.1002","volume":"119","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-2903-5554","authenticated-orcid":false,"given":"Benjamin","family":"Rich","sequence":"first","affiliation":[{"name":"InnoMx  Outremont Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2718-4335","authenticated-orcid":false,"given":"Meenakshi","family":"Srinivasan","sequence":"additional","affiliation":[{"name":"GSK  Waltham Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0074-1938","authenticated-orcid":false,"given":"Yu Liu","family":"Ho","sequence":"additional","affiliation":[{"name":"GSK  Collegeville Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2186-7195","authenticated-orcid":false,"given":"Sandra A.G.","family":"Visser","sequence":"additional","affiliation":[{"name":"GSK  Collegeville Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5703-8315","authenticated-orcid":false,"given":"Geraldine","family":"Ferron\u2010Brady","sequence":"additional","affiliation":[{"name":"GSK  Collegeville Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7390-9712","authenticated-orcid":false,"given":"Georgios","family":"Vlasakakis","sequence":"additional","affiliation":[{"name":"GSK  Collegeville Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,7]]},"reference":[{"key":"e_1_2_11_1_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.26857"},{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2024.1382872"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2020.100691"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41408-017-0032-9"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-018-0028-x"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2022.103862"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2010.031831"},{"key":"e_1_2_11_8_1","unstructured":"Al\u2010Ali H.K. Guglielmelli P. Hamer\u2010Maansson J.E. Braunstein E.&Gupta V.The impact of new or worsening anemia on clinical outcomes in 2233 patients with myelofibrosis treated with ruxolitinib: results from the expanded\u2010access JUMP study. Presented at: 2024 European Hematology Association Congress; June 13\u201316 2024; Madrid Spain. Poster P1044."},{"key":"e_1_2_11_9_1","doi-asserted-by":"crossref","unstructured":"Mesa R.A.et al.Impact of transfusion burden on health\u2010related quality of life (HRQOL) and functioning in patients (pts) with myelofibrosis (MF): post hoc analysis of SIMPLIFY\u20101 (S1) and \u22122 (S2). Poster presented at: ASCO Annual Meeting 2023; June 2\u20138 2023; Chicago IL. Poster 7066.","DOI":"10.1200\/JCO.2023.41.16_suppl.7066"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-021-01157-4"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1110556"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3026(17)30088-1"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2017.5818"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)02036-0"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-023-01471-z"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.70018"},{"key":"e_1_2_11_17_1","unstructured":"Ojjaara (momelotinib).Prescribing information. GSK<https:\/\/gskpro.com\/content\/dam\/global\/hcpportal\/en_US\/Prescribing_Information\/Ojjaara\/pdf\/OJJAARA\u2010PI\u2010PIL.PDF> (2023). Accessed April 10 2025."},{"key":"e_1_2_11_18_1","unstructured":"Omjjara (momelotinib).Summary of product characteristics. GSK<https:\/\/www.ema.europa.eu\/en\/documents\/product\u2010information\/omjjara\u2010epar\u2010product\u2010information_en.pdf> (2024). 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